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Fosforilación y modulación de un receptor de kainato (GluR6) por la proteína quinasa dependiente de la cAMP y la
L Y Wang1, F A Taverna, X P Huang
1Department of Physiology, University of Toronto, Ontario, Canada.
Science (New York, N.Y.)
|February 19, 1993
Resumen
Adenosina 3 3 La adenosina es una sustancia
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los canales iónicos ligandos, específicamente los receptores de glutamato, son cruciales para la neurotransmisión excitatoria en el cerebro de los mamíferos.
- El receptor de glutamato activado por kainato, GluR6, juega un papel importante en la función sináptica.
Objetivo del estudio:
- Para investigar la modulación funcional del receptor GluR6 por la adenosina 3',5'-monofosfato dependiente de la proteína quinasa A (PKA).
- Para identificar los sitios específicos de fosforilación en GluR6 responsables de la potenciación mediada por PKA.
Principales métodos:
- Expresión de los receptores en las células renales embrionarias humanas.
- Registros electrofisiológicos de corrientes evocadas por kainato.
- Mutagénesis dirigida al sitio para alterar residuos específicos de serina (Ser684, Ser666).
- Aplicación del PKA y los péptidos inhibidores.
Principales resultados:
- Las corrientes evocadas por kainato mostraron una desensibilización rápida, que fue inhibida por las lectinas.
- La perfusión intracelular de corrientes de kainato potenciadas por PKA, un efecto bloqueado por un péptido inhibidor.
- La mutagenesis de Ser684 y Ser666 abolió la potenciación de PKA, con Ser684 identificado como un probable sitio de fosforilación preferido.
Conclusiones:
- La función del receptor de glutamato está modulada directamente por la fosforilación de proteínas a través de la PKA.
- La regulación dinámica de los receptores excitatorios a través de la fosforilación puede estar relacionada con los procesos de aprendizaje y memoria en el cerebro.
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